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Article ; Online: α-Synuclein Seeding Amplification Assay: A Breakthrough in Diagnosing Parkinson Disease?

Seibyl, John P

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2024 Volume 65, Issue 2, Page(s) 174–175

MeSH term(s)	Humans ; alpha-Synuclein ; Parkinson Disease/diagnostic imaging
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.123.266191
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: α-Synuclein PET and Parkinson Disease Therapeutic Trials: Ever the Twain Shall Meet?

Seibyl, John P

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2022 Volume 63, Issue 10, Page(s) 1463–1466

MeSH term(s)	Humans ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/therapy ; Positron-Emission Tomography ; alpha-Synuclein
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.122.263918
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: Imaging Biomarkers for Central Nervous System Drug Development and Future Clinical Utility: Lessons from Neurodegenerative Disorders.

Seibyl, John P

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2022 Volume 64, Issue 1, Page(s) 12–19

Abstract: Diseases of the central nervous system are common and often chronic conditions associated with significant morbidity. In particular, neurodegenerative disorders including Alzheimer and Parkinson disease constitute a major health and socioeconomic ... ...

Abstract	Diseases of the central nervous system are common and often chronic conditions associated with significant morbidity. In particular, neurodegenerative disorders including Alzheimer and Parkinson disease constitute a major health and socioeconomic challenge, with an increasing incidence in many industrialized countries with aging populations. Recent work has established the primary role of abnormal protein accumulation and the spread of disease-specific deposits in brain as a factor in neurotoxicity and disruption of functional networks. A range of therapeutics from small molecules to antibodies targeting these proteinopathies are now in phase 2 and phase 3 clinical trials. These studies are methodologically challenging because of difficulty in accurately diagnosing early disease, the slow and variable rates of progression between individuals, and efficacy measures that may be cofounded by symptomatic improvements due to treatment but not reflecting disease course modification. Further, the ideal candidates for these treatments would be at-risk, or premanifest, persons in whom the pathologic process of the neurodegenerative disorder has begun but who are clinically normal and extremely difficult to identify. Scintigraphic imaging with PET and SPECT in trials offers the opportunity to interrogate pathophysiologic processes such as protein deposition with high specificity. This review summarizes the current implementation of these imaging biomarkers and the implications for future management of neurodegenerative disorders and central nervous system drug development in general.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Parkinson Disease/metabolism ; Biomarkers/metabolism ; Central Nervous System Agents
Chemical Substances	Biomarkers ; Central Nervous System Agents
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.122.264773
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: What Is the Role of Dopamine Transporter Imaging in Parkinson Prevention Clinical Trials?

Seibyl, John Peter / Kuo, Phillip

Neurology

2022 Volume 99, Issue 7 Suppl 1, Page(s) 61–67

MeSH term(s)	Corpus Striatum/metabolism ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Humans ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/drug therapy ; Tomography, Emission-Computed, Single-Photon/methods
Chemical Substances	Dopamine Plasma Membrane Transport Proteins
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200786
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Ui II Zs.153: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Zs.MO 374: Show issues

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Article ; Online: Neurotheranostics: The Next Frontier for Health Span.

Losee, Meryam A / Seibyl, John P / Kuo, Phillip H

Journal of nuclear medicine technology

2023 Volume 51, Issue 4, Page(s) 266–270

Abstract: With an aging U.S. population, advancements in the treatment of Alzheimer disease (AD) and other neurodegenerative diseases are key to the maximization of health span. The recent approval of 2 antiamyloid antibodies, which decrease brain amyloid load, ... ...

Abstract	With an aging U.S. population, advancements in the treatment of Alzheimer disease (AD) and other neurodegenerative diseases are key to the maximization of health span. The recent approval of 2 antiamyloid antibodies, which decrease brain amyloid load, places us on the cusp of breakthrough therapies that target the mechanism of the disease rather than just treating the symptoms. Although the trials that led to these approvals studied patients with mild early symptoms, multiple ongoing trials have enrolled cognitively normal patients screened for AD biomarkers including risk factors for amyloid positivity, family history, and genetic markers. Thus, amyloid PET can help identify an at-risk population that can be enrolled for antiamyloid therapy to prevent AD symptoms from ever developing. In this review, we examine the paradigm of neurotheranostics and how PET biomarkers of amyloid, tau, inflammation, and neurodegeneration could characterize the pathologic stage of AD and therefore allow for personalized therapy.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Brain/diagnostic imaging ; Brain/metabolism ; Amyloid ; Biomarkers ; Head/pathology ; Amyloid beta-Peptides/metabolism ; Positron-Emission Tomography
Chemical Substances	Amyloid ; Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	189163-7
ISSN	1535-5675 ; 0091-4916
ISSN (online)	1535-5675
ISSN	0091-4916
DOI	10.2967/jnmt.123.265502
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Zs.B 2211: Show issues

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Article ; Online: Dopamine Transporter Availability in Early Parkinson's Disease is Dependent on Sunlight Exposure.

Booij, Jan / Tellier, Sem P / Seibyl, John / Vriend, Chris

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 11, Page(s) 2131–2135

Abstract: Background: Preliminary studies suggested seasonality of dopaminergic functioning, but it is unknown whether dopamine transporter (DAT) expression in humans is also dependent on the seasons. We, therefore, investigated seasonal and sunlight-dependent ... ...

Abstract	Background: Preliminary studies suggested seasonality of dopaminergic functioning, but it is unknown whether dopamine transporter (DAT) expression in humans is also dependent on the seasons. We, therefore, investigated seasonal and sunlight-dependent effects on DAT availability in early Parkinson's disease (PD) patients and healthy controls. Methods: DAT single-photon emission computed tomography scans (n = 730) were gathered from the Parkinson's Progression Marker Initiative (PPMI) database. We used global horizontal irradiance (GHI) as proxy for sun exposure/month and assessed associations between striatal DAT availability and season (autumn/winter versus spring/summer), GHI and latitude of the PPMI site. Results: In PD patients, DAT availability in the left caudate nucleus was higher in spring/summer (B [standard error (SE)] = 0.05 [0.02], P = 0.03) and positively associated with higher sun exposure (B [SE] = 0.59 [0.22] × 10 Conclusion: Striatal DAT availability may be influenced by daylight exposure. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
MeSH term(s)	Humans ; Corpus Striatum/metabolism ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Parkinson Disease/complications ; Sunlight ; Tomography, Emission-Computed, Single-Photon/methods
Chemical Substances	Dopamine Plasma Membrane Transport Proteins
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29597
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 238: Show issues

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Article ; Online: Statistical Considerations in the Design of Clinical Trials Targeting Prodromal Parkinson Disease.

Macklin, Eric A / Coffey, Christopher S / Brumm, Michael C / Seibyl, John Peter

Neurology

2022 Volume 99, Issue 7 Suppl 1, Page(s) 68–75

Abstract: Clinical trials testing interventions for prodromal Parkinson disease (PD) hold particular promise for preserving neuronal function and thereby slowing or even forestalling progression to overt PD. Selection of the appropriate target population and ... ...

Abstract	Clinical trials testing interventions for prodromal Parkinson disease (PD) hold particular promise for preserving neuronal function and thereby slowing or even forestalling progression to overt PD. Selection of the appropriate target population and outcome measures presents challenges unique to prodromal PD. We propose 3 clinical trial designs, spanning phase 2a, phase 2b, and phase 3 development, that might serve as templates for prodromal PD trials. The proposed phase 2a trial is of a 3-arm design of short duration and focuses on proof of concept with respect to target engagement and change in a motor outcome in a subset of prodromal participants who already manifest asymptomatic but measurable motor dysfunction as an exploratory aim. The proposed phase 2b trial suggests progression of dopamine transporter imaging specific binding ratio as a primary outcome evaluated annually over 2 years with phenoconversion to PD as a key secondary outcome. The proposed phase 3 trial is a large, simple design of a nutraceutical or behavioral intervention with remote administration and phenoconversion as the primary outcome. We then consider what additional data are needed in the short term to better design prodromal PD trials and examine what longer-term goals would accelerate discovery of safe and effective therapies for individuals at risk of PD. Clear and potentially context-specific definitions of phenoconversion and validation of intermediate endpoints are needed in the short term. The use of adaptive trial designs, master protocols, and research registries would help accelerate therapy development in the long term.
MeSH term(s)	Humans ; Parkinson Disease/complications ; Prodromal Symptoms
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200897
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Article: SPECT and PET in Atypical Parkinsonism.

Seibyl, John P

PET clinics

2010 Volume 5, Issue 1, Page(s) 65–74

Abstract: Parkinson disease (PD) is the prototypic movement disorder originally described by James Parkinson, and it accounts for about 80% of a group of related degenerative motor disorders collectively referred to as the parkinsonisms, Parkinson spectrum ... ...

Abstract	Parkinson disease (PD) is the prototypic movement disorder originally described by James Parkinson, and it accounts for about 80% of a group of related degenerative motor disorders collectively referred to as the parkinsonisms, Parkinson spectrum disorders, or Parkinson plus disorders, terms which are used interchangeably throughout this article. Much work with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in the movement disorders has focused on the dopamine system. There have been at least 3 different presynaptic dopaminergic targets that are used successfully to interrogate this system. Another approach may be is to assess the dynamics of dopamine release into the synapse by the use of reversible-bound PET tracers or SPECT tracers. Both dopaminergic and nondopaminergic imaging in the diagnosis of movement disorders are discussed in this article.
Language	English
Publishing date	2010-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2764575-7
ISSN	1879-9809 ; 1556-8598
ISSN (online)	1879-9809
ISSN	1556-8598
DOI	10.1016/j.cpet.2010.02.005
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Einzelsignatur: Show issues

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Article: Single-photon emission computed tomography and positron emission tomography evaluations of patients with central motor disorders.

Seibyl, John P

Seminars in nuclear medicine

2008 Volume 38, Issue 4, Page(s) 274–286

Abstract: Neuroimaging biomarkers in movement disorders during the past decade have served as diagnostic agents (Europe), tools for evaluation of novel therapeutics, and a powerful means for describing pathophysiology by revealing in vivo changes at different ... ...

Abstract	Neuroimaging biomarkers in movement disorders during the past decade have served as diagnostic agents (Europe), tools for evaluation of novel therapeutics, and a powerful means for describing pathophysiology by revealing in vivo changes at different stages of disease and within the course of an individual patient's illness. As imaging with agents tracking dopaminergic function become more available, the next decade promises to enhance our clinical sophistication in the optimal use of dopaminergic imaging biomarkers for differential diagnosis, characterization of at-risk populations, guiding selection and management of appropriate treatments. The clinical role of these agents as clinical tools goes hand in hand with the development and availability of disease-modifying drugs, which carry the additional requirement for early and accurate diagnosis and improved clinical monitoring once treatment is initiated. Challenges remain in the ideal application of neuroimaging in the clinical algorithms for patient assessment and management. Further, the application of imaging to other targets, both monamineric and nonmonoaminergic, could serve a function beyond the important delineation of pathologic change occurring in patients with Parkinson's disease to suggest some role in improved phenotyping and classification of patients with Parkinson's disease presenting with different symptom clusters. New areas of focus based on the elucidation of mechanisms at the cellular and molecular level, including intense interest in alpha-synuclein and other protein inclusions in neurons and glia, have piqued interest in their in vivo assessment using scinitigraphic methods. Perhaps ultimately, treatment that is targeted to a better delineated pathophysiology-based characterization of movement disorder patients will emerge. The application of neuroimaging biomarkers to multiple ends in movement disorders provides an important model for the multiple roles diagnostic imaging agents can serve in neurodegenerative disorders; for diagnosis, for elaborating pathophysiology in patient populations, for developing new drugs, ultimately for improving clinical management.
MeSH term(s)	Brain/diagnostic imaging ; Brain Diseases/diagnostic imaging ; Humans ; Image Enhancement/methods ; Movement Disorders/diagnostic imaging ; Positron-Emission Tomography/trends ; Radioisotopes ; Radiopharmaceuticals ; Tomography, Emission-Computed, Single-Photon/trends
Chemical Substances	Radioisotopes ; Radiopharmaceuticals
Language	English
Publishing date	2008-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	120248-0
ISSN	0001-2998
ISSN	0001-2998
DOI	10.1053/j.semnuclmed.2008.03.001
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Zs.A 763: Show issues

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Article ; Online: Clinical and Imaging Progression in the PARS Cohort: Long-Term Follow-up.

Siderowf, Andrew / Jennings, Danna / Stern, Matthew / Seibyl, John / Eberly, Shirley / Oakes, David / Marek, Kenneth

Movement disorders : official journal of the Movement Disorder Society

2020 Volume 35, Issue 9, Page(s) 1550–1557

Abstract: Background and objectives: The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression ... ...

Abstract	Background and objectives: The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression markers during the prodromal period. Methods: Subjects with hyposmia completed annual clinical evaluations and biennial [ Results: Over a mean of 6.3 [standard deviation: 2.2] years of follow-up, 67% (n = 14) of dopamine transporter deficit subjects, 20% (n = 6) of dopamine transporter indeterminate subjects, and 4% (n = 6) of dopamine transporter normal subjects converted to a PD diagnosis (P < 0.0001). Among subjects without dopamine transporter deficit at baseline, a reduction to ≤65% age-expected uptake occurred in 12 of 30 (40%) with indeterminate dopamine transporter and 7 of 134 (5%) with no dopamine transporter DAT deficit (P < 0.0001). Imaging conversion during follow-up was associated with subsequent clinical conversion (hazard ratio: 9.6; P = 0.0157). Discussion and conclusions: Long-term follow-up of the PARS cohort demonstrated a high rate of conversion to clinical PD in subjects who either had abnormal dopamine transporter imaging at baseline or developed abnormal imaging during follow-up. These data extend the earlier PARS findings and present new results showing the sequence of incident imaging deficit, imaging progression, and clinical changes that occur in prodromal PD. © 2020 International Parkinson and Movement Disorder Society.
MeSH term(s)	Cohort Studies ; Dopamine Plasma Membrane Transport Proteins ; Follow-Up Studies ; Humans ; Parkinson Disease/diagnostic imaging ; Prodromal Symptoms ; Tomography, Emission-Computed, Single-Photon
Chemical Substances	Dopamine Plasma Membrane Transport Proteins
Language	English
Publishing date	2020-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.28139
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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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